Review articleCD147/basigin promotes progression of malignant melanoma and other cancers
Introduction
Malignant cancers are characterized by immortalized cellular proliferation, activated invasiveness into the surrounding stroma, distant metastasis, and angiogenesis via vascular endothelial growth factor (VEGF) production. Cancer cells often acquire resistance to anticancer drugs; these cells are of the multi-drug resistance (MDR) phenotype. Distant metastasis and MDR, the major obstacles to the effective treatment of malignant cancers, remain to be overcome.
CD147/basigin (Bsg), an integral plasma membrane protein belonging to the immunoglobulin superfamily, is expressed widely in various embryonic and adult tissues [1], [2]. Because of its ubiquitous distribution, it is thought to play fundamental roles in the regulation of various cellular activities. Molecules identical to Bsg were discovered and given different names, i.e. M6 [3] and EMMPRIN [4] in humans, HT7 [5], neurothelin [6], and 5A11 [7] in chickens, pg42 [8] in mice, and OX-47 [9] and CE9 [10] in rats. They turned out to be multifunctional and involved in various physiological processes such as fetal development, reproduction, T cell differentiation, and neural and retinal functions [11], [12]. There is growing evidence that Bsg expression is highly increased in various tumor cells [13], [14], [15], [16], [17], [18], [19] including malignant melanoma (MM) [20]. The elevated expression of Bsg in cancer cells suggests it as a pivotal regulator of tumorigenesis. Indeed, Bsg was found to be functionally involved in tumor invasiveness, metastasis, growth, and angiogenesis and to regulate glycolysis and MDR [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31]. Here we review the function of Bsg in regulating tumor progression in human malignant tumors including MM.
Section snippets
Cloning of CD147/basigin and related molecules
Cell surface glycoproteins regulate cellular growth and differentiation and serve as surface markers. The cell surface marker Lewis X antigen is expressed in embryonal carcinoma (EC) cells; it is not found in most cells differentiated from EC cells. CD147/basigin, identified as a new member of the immunoglobulin (Ig) superfamily, was initially cloned as a carrier of Lewis X carbohydrate antigen in teratocarcinoma stem cells in a study of a developmentally regulated cell surface marker [1]. We
Invasiveness of malignant melanoma
The possible role of CD147 in invasion in association with MMP expression was investigated using human MM specimens and the human MM cells KHm-1/IV and G361, that highly express CD147 compared to normal human melanocytes (NHMCs). Immunohistochemically, there are significant positive correlations between the level of CD147 expression in MM cells and the expression of MMPs; MMP-1 (collagenase), MMP-2 (gelatinase), MMP-3 (stromelysine), and MT1-MMP (membrane type MMP) in fibroblasts surrounding
CD147/basigin and glycolysis
CD147 is an important molecule for tumor progression including tumor invasiveness, metastasis, proliferation, and angiogenesis. The common mechanisms underlying these functions have been addressed.
Glycolysis is enhanced in tumor cells [40]. Under physiological conditions, it is the result of an anaerobic enzymatic conversion of glucose to pyruvate or lactate to produce energy stored in the form of adenosine triphosphate (ATP). Warburg [41] first reported that cancer cells depend on glycolysis
CD147/basigin and multi-drug resistance
Multi-drug resistance and metastasis, the major obstacles to the effective treatment of malignant cancers, have been studied extensively and the functional linkage between these two phenotypes has been reported. Yang and co-workers [27], [28] who used a human mammary carcinoma cell line (MCF7) and its MDR counterpart (MCF7/Adr) found that CD147 connects these two phenotypes. The MDR phenotype of MCF7/Adr cells is primarily attributable to P-glycoprotein (P-gp), an ATP-dependent transmembrane
Conclusion
CD147, originally cloned as a carrier of Lewis X carbohydrate antigen in a study of a developmentally regulated cell surface antigen, plays important roles in the various processes of tumor progression including cellular proliferation, invasiveness, metastasis, angiogenesis, tumor cell glycolysis, and MDR phenotypes, emerging as a potential target for cancer therapy. However, additional studies to induce the localized expression of CD147 in cancer cells are needed because CD147-null mice show
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2020, Bioorganic ChemistryCitation Excerpt :CD147 is a transmembrane glycoprotein and a member of immunoglobulin superfamily [3,4]. It is a tumor-associated antigen that is highly expressed in various tumors, including malignant melanoma (MM) [5–10]. CD147, which is also called extracellular matrix metalloproteinase inducer (EMMPRIN), overexpression of CD147 has a significant association with the expression of matrix metalloproteinase (MMP), and it also reported to be an association with vascular endothelial growth factor (VEGF) [10–12].
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